Similarities and differences between Alzheimer's disease and vascular dementia from the viewpoint of nutrition.Otsuka M: Department of Neurology, Jichi Medical School, Omiya Medical Center; Yamaguchi K, Ueki AAnn N Y Acad Sci 2002 Nov 977:155-61AbstractDietary habits were compared in patients with Alzheimer's disease (AD) and those with vascular dementia (VaD). Twenty-seven patients with AD, 15 patients with VaD, and 49 age-matched controls were enrolled. Nutritional status was assessed using a semiquantified food-frequency questionnaire. Dietary habits were very similar in male patients with AD and VaD. Both groups had significantly higher energy intake than their energy demands: +25% for AD and +35% for VaD, respectively. However, major sources of energy were different: grains and animal fats for AD versus only grains for VaD. Calculation of nutrients revealed excess intake of n-6 polyunsaturated fatty acids (PUFA) and relative deficiencies of multiple vitamins including antioxidants, vitamin C and carotene, and the vitamin B group. In contrast, dietary habits in female patients with AD differed significantly from those of male patients. Female patients consumed significantly lower amounts of fish and green vegetables. Calculation of nutrients showed absolute deficiencies of n-3 PUFA, multiple vitamins, and minerals. Our results show that AD and VaD are similar from the viewpoint of nutrition, except for the higher consumption of animal fats for AD patients, probably reflecting Westernization of dietary habits in recent years. Nutrition may be relevant to the pathogenesis of dementia through many processes. Higher intake of energy and lower intake of antioxidants may exaggerate the process of dementia through oxidative stress. Excessive amounts of n-6 PUFA or deficiency of n-3 PUFA may cause chronic inflammation, platelet aggregation, or endothelial dysfunction of microvasculature. Nutrition may be useful for preventing dementia, although gender-specific differences must be taken into account.

Analysis of dietary factors in Alzheimer's disease: clinical use of nutritional intervention for prevention and treatment of dementia.Otsuka M: Department of Neurology, Jichi Medical School, Omiya Medical CenterNippon Ronen Igakkai Zasshi 2000 Dec 37:970-3AbstractTo determine dietary factors involved in the pathological process of Alzheimer's disease (AD), we analyzed food consumption and intake of nutrients using Self-administered Diet History Questionnaire (DHQ) developed for Japanese. Sixty four AD patients and 80 age-matched healthy subjects were enrolled in this study. AD was diagnosed according to the criteria of DSM-IV. Dietary behaviors of AD patients was markedly deviated from those of age-matched healthy elderly. AD patients disliked fish and green-yellow vegetables and took more meats than controls. Energy-adjusted analysis of nutrients revealed that AD patients took less vitamin C and carotene. Most conspicuously, AD patients took significantly smaller amount of n-3 polyunsaturated fatty acid (PUFA) reflecting low consumption of fish, and their n-6/n-3 ratio was significantly increased. These habits started from 3 months to 44 years before the onset of dementia, suggesting these dietary abnormalities are not merely the consequence of dementia. Rather, it implies that AD might be a life style-related disease such as coronary heart disease, western style diet-associated cancer and hyperallergy. To see if cognitive function was improved by correcting the n-6/n-3 ratio, we prescribed eicossapentaenoic acid (EPA), one type of n-3 PUFA, for AD patients. Cognitive function was evaluated using MMSE. Administration of EPA (900 mg/day) improved MMSE significantly with maximal effects at 3 months and the effects lasted 6 months. However, the score of MMSE decreased after 6 months. The present study showed that nutritional intervention is useful for the prevention of AD, and also for the therapy of dementia, though it has some limitation.

The beta-oxidation of arachidonic acid and the synthesis of docosahexaenoic acid are selectively and consistently altered in skin fibroblasts from three Zellweger patients versus X-adrenoleukodystrophy, Alzheimer and control subjects.Petroni A: Institute of Pharmacological Sciences, University of Milan, Italy; Bertagnolio B, La Spada P, Blasevich M, Papini N, Govoni S, Rimoldi M, Galli CNeurosci Lett 1998 Jul 250:145-8AbstractThe beta-oxidation of [3H] arachidonic acid (AA; 20:4 n-6) and the conversion of [1-14C]eicosapentaenoic acid (EPA, 20:5 n-3) to docosahexaenoic acid (DHA, 22:6 n-3) have been studied in skin fibroblasts from patients with inherited peroxisomal diseases, such as Zellweger (ZW) and X-linked adrenoleukodystrophy (X-ALD), from patients with Alzheimer's disease (AD), a non-inherited neuropathology, and from controls. EPA is not converted to DHA, while there is enhanced formation of the intermediate product 22:5 n-3 in ZW, when compared to X-ALD, AD and controls. We also confirmed that AA is not beta-oxidized to 4,7,10-hexadecatrienoic acid (16:3), a metabolite produced by peroxisomes, while being more effectively converted to the elongation product 22:4, in ZW, in comparison to X-ALD, AD and controls. The data demonstrate a defect in DHA synthesis and in AA beta-oxidation, and the occurrence of associated adaptative modifications in the metabolism of these long chain PUFA, in three Italian ZW patients.

Essential fatty acids and the brain: possible health implications.Youdim KA: Laboratory of Neuroscience, United States Department of Agriculture, Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Martin A, Joseph JAInt J Dev Neurosci 2000 Jul-Aug 18:383-99AbstractLinoleic and alpha-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions affecting membrane fluidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs reflect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit.

Fatty acids of plasma lipids, red cells and platelets in Alzheimer's disease and vascular dementia.Tilvis RS, Erkinjuntti T, Sulkava R, Miettinen TAAtherosclerosis 1987 Jun 65:237-45AbstractFatty acids of plasma lipids, red cells and platelets were analyzed from 38 demented patients (age 53-88 years), comprising 11 patients with Alzheimer's disease (AD), 19 with multi-infarct dementia (MID) and 8 with probable vascular dementia (PVD). The mean age, body mass index, duration of dementia and content of triglycerides, total cholesterol and HDL-cholesterol in plasma were similar in AD and MID. The patients with PVD were older. As compared to AD, in MID and PVD the linoleic acid (LA) and other n-6 and n-3 polyunsaturated fatty acids (PUFA) were significantly lower in red cells and tended to be lower also in serum triglycerides, cholesterol esters (CHE) and phospholipids (PL), and platelets. The LA content of red cells was significantly correlated with that of serum CHE and PL, and n-6 PUFA (including arachidonic acid) of red cells. The low LA content of red cells was associated with old age, coronary heart disease and heart failure, but not with the severity of dementia.

Dietary fat intake and the risk of incident dementia in the Rotterdam Study.Kalmijn S: Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands; Launer LJ, Ott A, Witteman JC, Hofman A, Breteler MMAnn Neurol 1997 Nov 42:776-82AbstractA high intake of saturated fat and cholesterol and a low intake of polyunsaturated fatty acids have been related to an increased risk of cardiovascular disease. Cardiovascular disease has been associated with dementia. We investigated the association between fat intake and incident dementia among participants, age 55 years or older, from the population-based prospective Rotterdam Study. Food intake of 5,386 nondemented participants was assessed at baseline with a semiquantitative food-frequency questionnaire. At baseline and after an average of 2.1 years of follow-up, we screened for dementia with a three-step protocol that included a clinical examination. The risk of dementia at follow-up (RR [95% CI]) was assessed with logistic regression. After adjustment for age, sex, education, and energy intake, high intakes of the following nutrients were associated with an increased risk of dementia: total fat (RR = 2.4 [1.1-5.2]), saturated fat (RR = 1.9 [0.9-4.0]), and cholesterol (RR = 1.7 [0.9-3.2]). Dementia with a vascular component was most strongly related to total fat and saturated fat. Fish consumption, an important source of n-3 polyunsaturated fatty acids, was inversely related to incident dementia (RR = 0.4 [0.2-0.91), and in particular to Alzheimer's disease (RR = 0.3 [0.1-0.9]). This study suggests that a high saturated fat and cholesterol intake increases the risk of dementia, whereas fish consumption may decrease this risk.

Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis.Martinez M: Biomedical Research Unit, University Maternity-Children's Hospital, Barcelona, SpainLipids 1996 Mar 31 Suppl:S145-52AbstractA patient with classic Zellweger syndrome was treated with docosahexaenoic acid ethyl ester (DHA-EE) for three months. Five other patients with Zellweger variants (four of them less than one-year-old and a five-year-old) were treated with DHA-EE until normalization of the DHA levels in erythrocytes. When arachidonic acid (AA) concentration decreased, AA was added to the diet. Thereafter, a combined treatment with DHA plus AA followed, in a variable proportion that allowed the high levels of DHA in erythrocytes to be maintained. In the patient with Zellweger syndrome, DHA therapy produced an increase in plasmalogen and a decrease in 26:0 and 26:1. No clear clinical improvement could be detected in this patient during the short period of treatment with DHA-EE. The most consistent clinical effect produced by DHA therapy in the other patients with disorders of peroxisomal biogenesis was visual improvement, even in those patients that were virtually blind before the treatment. In general, the developmental curve began to accelerate. The infants became more alert, acquired better visual and social contact and muscular tone improved, with the beginning of good head control. The liver tests tended to normalize and some patients showed a reduction of hepatomegaly. All these favorable changes occurred when the patients were taking the DHA-EE alone. In some of the patients, muscular tone seemed to improve further after introducing AA supplements. From the biochemical point of view, the plasmalogen levels increased in most cases in erythrocytes, and the two ratios 26:0/22:0 and 26:1/22:0 decreased in plasma. In some patients there was a tendency for 26:1 to increase in plasma and for 18:0 plasmalogen to decrease in erythrocytes when AA was introduced in the diet. The significance of these findings remains to be elucidated, but they stress the importance of strict monitoring and control of the polyunsaturated fatty acids status during DHA therapy.

Fatty acid analysis of blood plasma of patients with Alzheimer's disease, other types of dementia, and cognitive impairment.Conquer JA: Department of Human Biology and Nutritional Sciences, University of Guelph, Ontario, Canada; Tierney MC, Zecevic J, Bettger WJ, Fisher RHLipids 2000 Dec 35:1305-12AbstractFatty acid differences, including docosahexaenoic acid (DHA; 22:6n-3) have been shown in the brains of Alzheimer's patients (AD) as compared with normal age-matched individuals. Furthermore, low serum DHA is a significant risk factor for the development of AD. The relative concentration of DHA and other fatty acids, however, in the plasma of AD patients compared with patients with other kinds of dementias (other dementias; OD), patients who are cognitively impaired but nondemented (CIND), or normal patients is not known. In this study we analyzed the total phospholipid, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (lysoPC) fractions of plasma from patients diagnosed with AD, OD, or CIND and compared them with a group of elderly control subjects with normal cognitive functioning. Plasma phospholipid and PC levels of 20:5n-3, DHA, total n-3 fatty acids, and the n-3/n-6 ratio were lower in the AD, OD, and CIND groups. Plasma phospholipid 24:0 was lower in the AD, OD, and CIND groups as compared with the group of control patients, and total n-6 fatty acid levels were higher in the AD and CIND groups only. In the plasma PE fraction, levels of 20:5n-3, DHA, and the total n-3 fatty acid levels were significantly lower in the AD, OD, and CIND groups. DHA levels were lower in the lysoPC fraction of CIND individuals only. There were no other differences in the fatty acid compositions of the different phospholipid fractions. Therefore, in AD, OD, and CIND individuals, low levels of n-3 fatty acids in the plasma may be a risk factor for cognitive impairment and/or dementia. Interestingly, a decreased level of plasma DHA was not limited to the AD patients but appears to be common in cognitive impairment with aging.